AIM1 promoter hypermethylation as a predictor of decreased risk of recurrence following radical prostatectomy

作者：Rosenbaum Eli; Begum Shahnaz; Brait Mariana; Zahurak Marianna; Maldonado Leonel; Mangold Leslie A; Eisenberger Mario A; Epstein Jonathan I; Partin Alan W; Sidransky David; Hoque Mohammad O^*

来源：Prostate, 2012, 72(10): 1133-1139.

DOI：10.1002/pros.22461

• prostate cancer
• DNA methylation
• risk of recurrence
• biomarker

PURPOSE To evaluate the prognostic significance of six epigenetic biomarkers (AIM1, CDH1, KIF1A, MT1G, PAK3, and RBM6 promoter hypermethlation) in a homogeneous group of prostate cancer patients, following radical prostatectomy (RP). PATIENTS AND METHODS Biomarker analyses were performed retrospectively on tumors from 95 prostate cancer patients all with a Gleason score of 3?+?4?=?7 and a minimum follow-up period of 8 years. Using Quantitative Methylation Specific PCR (QMSP), we analyzed the promoter region of six genes in primary prostate tumor tissues. Time to any progression was the primary endpoint and development of metastatic disease and/or death from prostate cancer was a secondary endpoint. The association of clinicopathological and biomolecular risk factors to recurrence was performed using the Log-rank test and Cox proportional hazards model for multivariate analysis. To identify independent prognostic factors, a stepwise selection method was used. RESULTS At a median follow-up time of 10 years, 48 patients (50.5%) had evidence of recurrence: Biochemical/PSA relapse, metastases, or death from prostate cancer. In the final multivariate analysis for time to progression, the significant factors were: Older age, HR?=?0.95 (95% CI: 0.91, 1.0) (P?=?0.03), positive lymph nodes HR?=?2.11 (95% CI: 1.05, 4.26) (P?=?0.04), and decreased hypermethylation of AIM1 HR?=?0.45 (95% CI: 0.2, 1.0) (P?=?0.05). CONCLUSIONS Methylation status of AIM1 in the prostate cancer specimen may predict for time to recurrence in Gleason 3?+?4?=?7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort. Prostate 72:11331139, 2012.

• 出版日期2012-7